Fig. 3.

Role of IFN‐γ in host immunity to microbes. Intramacrophagic pathogens (such as mycobacteria) infect macrophages and strongly induce production of IL‐12, which binds IL‐12 receptors (IL‐12Rβ1 and IL‐12Rβ2 heterodimer) and activates T/NK cells to produce IFN‐γ. IFN‐γ then binds IFN‐γ receptors (IFNGR1 and IFNGR2 heterodimer), enabling STAT1 activation and expression of ISGs to eliminate the engulfed microbes. IFN‐γ also stimulates other cell types to induce ISG expression in a similar way. Anti‐IFN‐γ autoantibodies have been identified in adult patients with disseminated mycobacterial infections [18]. The direct role of IFN‐γ in antiviral responses has not been established. During viral infection, cells recognize viral invasion through PRRs and they produce pro‐inflammatory cytokines. The pro‐inflammatory cytokines further enhance IFN‐γ production. The synergistic effects of IFN‐γ and pro‐inflammatory cytokines may orchestrate the host immune system to tackle the viral invasion. However, hyperactivity of this pro‐inflammatory response may also cause cytokine release syndrome and cause host tissue damage. Thus, blocking these over‐reacting cytokine responses by means of anticytokine antibodies, such as anti‐IFN‐γ antibodies, might have a clinical benefit.